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BLOODTRANSFUSION
COMPLICATIONS
Dr abdullah alzahrani
INTRODUCTION
■ Transfusions of red blood cells are given to children
in a wide variety of clinical settings.
■ Children with anemia due to congenital or acquired
disease, blood loss from trauma or surgery, or (in
the case of premature infants) blood sampling.
■ On the other hand, red cell transfusion has
significant risks, including volume overload,
transmission of infectious agents, and transfusion
reactions.
■ Transfusion reaction
– Acute hemolytic reactions
– Delayed hemolytic reactions
– Febrile reactions
– Allergic and anaphylactic reactions
– Transfusion-associated lung injury
■ Infection
■ Circulatory overload
■ Metabolic toxicity
■ Graft-versus-host disease
■ Iron overload
Acute hemolytic reactions
■ Medical emergency that results from the rapid
destruction of donor erythrocytes by preformed
recipient antibodies.
■ usually result from the mistransfusion of ABO-
incompatible red cells.
■ More typically occur when a group O recipient is
transfused with non-group O red cells.
■ These reactions involve naturally occurring IgM anti-
A and anti-B, which fix complement and cause rapid
intravascular hemolysis.
Acute hemolytic reactions
■ Fever and chills may be the only manifestations and,
in patients under anesthesia or in coma, DIC may be
the presenting mode, with oozing of blood from
puncture sites and hemoglobinuria.
■ direct antiglobulin (Coombs) test will be positive,
unless all of the transfused red cells have already
been destroyed and/or removed at the time of
testing.
■ This complication is best prevented, rather than
treated, by meticulous attention to patient and
sample identification.
Acute hemolytic reactions :
treatment
■ Stop the transfusion, but leave the intravenous line attached.
■ The bag containing the transfused cells, along with all attached
labels, should not be discarded, as repeat typing and cross-
matching of this unit by the blood bank will most likely be
required.
■ Maintain the patient's airway, blood pressure, and heart rate.
■ Begin generous fluid replacement immediately to initiate a
diuresis and avoid hypotension
■ From the other arm, obtain a sample for a direct antiglobulin
test, plasma free hemoglobin, and repeat type and cross-
match. Save a urine sample for hemoglobin testing.
Acute hemolytic reactions :
treatment
■ Avoid the use of Ringer's lactate solution because its content of
calcium may initiate clotting of any blood remaining in the
intravenous line.
■ Avoid dextrose-containing solutions because the dextrose
may hemolyze any of the remaining red cells in the line.
■ The blood bank should be alerted immediately, and a search
for clerical error should be instituted.
■ Every hospital has a protocol for evaluating transfusion
reactions, which should be rigorously followed.
Delayed hemolytic reactions
■ Delayed hemolysis results when the patient produces an
antibody days following a blood transfusion
■ It presents 2 to 10 days following transfusion as jaundice
and/or an unexpected fall in hemoglobin.
■ A delayed hemolytic transfusion reaction is confirmed by
repeat antibody screening of the patient's plasma, which
demonstrates the presence of a specific alloantibody that was
not previously present.
Delayed hemolytic reactions
■ Positive direct antiglobulin test for IgG with a positive
eluate against the corresponding antigen will confirm the
diagnosis.
■ It is therefore important to make the diagnosis, inform
the patient of the name of the offending antigen, and
maintain appropriate hospital and blood bank records.
■ Subsequent red cell transfusions should utilize blood
that tests negative for the newly identified antigen.
■ No treatment is required in the absence of brisk
hemolysis
Febrile reactions
■ most common transfusion reaction is a febrile, nonhemolytic
transfusion reaction (FNHTR).
■ The clinical manifestations : fever, often a chill, and sometimes
mild dyspnea . within one to six hours after transfusion of red
cells or platelets.
■ FNHTRs are benign, causing no lasting sequelae, but are
uncomfortable and sometimes frightening to the patient.
Furthermore, since fever, may be the sign of a severe, acute
hemolytic transfusion reaction
Febrile reactions
■ It is now clear that FNHTRs are commonly caused by
cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor
necrosis factor-alpha (TNFa), which are generated and
accumulate during the storage of blood components
■ Treatment includes stopping the transfusion and excluding a
hemolytic reaction or sepsis as the cause of fever.
■ Antipyretic therapy is given for symptomatic relief.These
reactions are reduced with leukoreduction (reduce the number
of leukocytes transfused)
Acetaminophen and antihistamine
premedication
■ A 2007 review summarized the data from studies that
evaluated the use of premedication to decrease the incidence
of FNHTRs or allergic transfusion reactions
■ Despite the fact that these medications are frequently ordered
prior to transfusion, the authors concluded that there is no
evidence to support the use of premedication with
antihistamines and/or acetaminophen for the prevention of
these reactions.
TobianAA, King KE, Ness PM.Transfusion premedications: a growing practice not
based on evidence.Transfusion 2007; 47:1089.
Acetaminophen and antihistamine
premedication
■ This conclusion was supported by a subsequent randomized,
double-blind, placebo-controlled study of transfusion
reactions in 315 hematology/oncology patients scheduled to
receive leukocyte filtered blood products
■ Patients received acetaminophen 500 mg plus 25 mg
diphenhydramine or matching placebos 30 minutes before
transfusion and were monitored for the following four hours.
■ There was no significant difference in the overall risk of
transfusion reactions between the treatment and placebo
groups (1.4 versus 1.5 reactions/100 transfusions, respectively).
Kennedy LD,Case LD, Hurd DD, et al.A prospective, randomized, double-blind controlled trial of
acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention
of transfusion reactions.Transfusion 2008; 48:2285.
Allergic and anaphylactic reactions
■ An anaphylactic, allergic, or anaphylactoid reaction to a blood
transfusion can vary in severity from mild hives and itching to
fatal anaphylaxis. manifested by shock, hypotension,
angioedema, and respiratory distress
■ While more common with plasma and platelet transfusions,
these reactions also may occur following red cell transfusion.
■ may occur within a few seconds to a few minutes following
the initiation of a transfusion, It is the rapid onset that is
characteristic of an ATR
Allergic and anaphylactic reactions
■ Treatment is
– Immediate cessation of the transfusion
– Epinephrine intramuscularly
– Resuscitation of hypotensive patients with intravenous
fluids
– Preparation, for possible administration, of an intravenous
epinephrine
– Airway maintenance, oxygenation
– Vasopressors (eg, dopamine), if necessary
Transfusion-associated lung injury
■ The presence of transfusion-associated acute lung injury
(TRALI) should be suspected when dyspnea, bilateral non
cardiogenic pulmonary edema, hypotension, and fever occur
within six hours of completion of transfusion.
■ TRALI is the leading cause of transfusion-related mortality in
the United States.
■ It is due primarily to the interaction between leukocytes from
the recipient and anti-HLA antibodies or antigranulocyte
antibodies from the donor.
■ Treatment is supportive.
Infection
■ All donated blood is extensively screened for transfusion-
transmitted infections; as a result, the risk of acquiring infection is
extremely low
■ Each unit of blood administered is screened for a number of
infections, including HIV, hepatitis B and C viruses.
■ Residual risk remains largely from "window period" donations,
during the time when antigen and/or antibody are of such low level
as to be undetectable by current techniques.
■ The risk of bacterial contamination of blood products is much
greater than the risk of viral transmission.
■ Fever , hypotension, or other signs of sepsis should be
investigated carefully in a patient who has received a transfusion.
Circulatory overload
■ Transfusion-associated circulatory overload (TACO) may occur in
children, although it is more common in adults.
■ Manifestations may begin near the end or within six hours of the
transfusion.
■ Patients should be monitored closely during this time period for
suggestive signs and symptoms, including dyspnea, tachycardia,
and a wide pulse pressure, often with hypertension.
■ Patients deemed to be at risk for volume overload (such as those
with impaired cardiac function) can be transfused at a slower rate
and diuretic therapy (eg, furosemide 0.5 to 1 mg/kg per dose) may
be used as a prophylactic measure and/or for treatment of
symptoms.
Circulatory overload
■ The symptoms of TACO are similar to those of TRALI.
Distinguishing features are as follows:
– TACO usually is associated with transfusion of a large volume
of blood or a high rate of infusion; TRALI may occur with
relatively small volumes at a slow rate
– Hypertension is commonly seen in TACO but is uncommon in
TRALI.
– Fever is typically absent in TACO whereas TRALI is often
associated with fever.
– Brain natriuretic peptide (BNP) is often elevated in patients
with TACO whereas it may be normal in TRALI.
– Patients with TACO usually responds well to diuretic therapy;
the response to diuretic therapy in patients with TRALI is
variable.
Metabolic toxicity
■ Hypocalcemia and/or hypoglycemia, which results from the
infused citrate in the preservative solution. Newborns are at
particular risk for this complication.
■ Hyperkalemia in patients who receive large volumes of blood
(eg, exchange or massive transfusions) or irradiated blood
(radiation increases cellular leakage of potassium).
■ Clinically significant accumulation of mannitol (a component of
preservative solutions) in neonates who receive large volumes
of blood may result in an osmotic diuresis.
■ Clinically significant accumulation of adenine (a component of
preservative solutions) in neonates who receive large volumes
of blood may cause nephrotoxicity.
Graft-versus-host disease
■ Transfusion-associated graft-versus-host disease (TA-GVHD) is
almost universally fatal and can be prevented by use of
irradiated products.
■ It is caused by viable, competent donor lymphocytes
■ To reduce the risk ofTA-GVHD in patients requiring red blood
cell transfusion, it is important to consider the immune status
of the child and use irradiated products if indicated
■ Patients who are at risk forTA-GVHD include premature, low
birth weight infants, infants and children with primary
immunodeficiencies, organ transplant recipients, and
patients receiving chemotherapy or other
immunosuppressive therapy.
Indication for irradiation of cellular blood
components for the prevention of
transfusion-associated graft-versus-host
disease
■ Immunocompromised hematopoietic stem cell recipients or
organ transplant recipients
■ Patients with hematologic disorders who will be undergoing
marrow transplantation imminently
■ Intrauterine transfusion
■ Neonatal exchange transfusions
■ Premature, low birthweight neonates
■ Hodgkin lymphoma
■ Congenital cell-mediated immunodeficiencies
Iron overload
■ Iron overload can be a significant problem in children who are
transfused chronically.
■ As an example, the main cause of death in patients with
thalassemia major is heart failure or fatal arrhythmia due to
deposition of transfused iron in the heart.
■ Children who are at risk for iron overload can be treated with
iron chelation therapy. It can reduce the damage produced by
the life-long need for red cell transfusions in these children.
■ In addition, exchange transfusion rather than simple
transfusion has been used in children with sickle cell disease,
partly to reduce the risk of iron overload.

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Blood transfusion complications

  • 2. INTRODUCTION ■ Transfusions of red blood cells are given to children in a wide variety of clinical settings. ■ Children with anemia due to congenital or acquired disease, blood loss from trauma or surgery, or (in the case of premature infants) blood sampling. ■ On the other hand, red cell transfusion has significant risks, including volume overload, transmission of infectious agents, and transfusion reactions.
  • 3. ■ Transfusion reaction – Acute hemolytic reactions – Delayed hemolytic reactions – Febrile reactions – Allergic and anaphylactic reactions – Transfusion-associated lung injury ■ Infection ■ Circulatory overload ■ Metabolic toxicity ■ Graft-versus-host disease ■ Iron overload
  • 4. Acute hemolytic reactions ■ Medical emergency that results from the rapid destruction of donor erythrocytes by preformed recipient antibodies. ■ usually result from the mistransfusion of ABO- incompatible red cells. ■ More typically occur when a group O recipient is transfused with non-group O red cells. ■ These reactions involve naturally occurring IgM anti- A and anti-B, which fix complement and cause rapid intravascular hemolysis.
  • 5. Acute hemolytic reactions ■ Fever and chills may be the only manifestations and, in patients under anesthesia or in coma, DIC may be the presenting mode, with oozing of blood from puncture sites and hemoglobinuria. ■ direct antiglobulin (Coombs) test will be positive, unless all of the transfused red cells have already been destroyed and/or removed at the time of testing. ■ This complication is best prevented, rather than treated, by meticulous attention to patient and sample identification.
  • 6. Acute hemolytic reactions : treatment ■ Stop the transfusion, but leave the intravenous line attached. ■ The bag containing the transfused cells, along with all attached labels, should not be discarded, as repeat typing and cross- matching of this unit by the blood bank will most likely be required. ■ Maintain the patient's airway, blood pressure, and heart rate. ■ Begin generous fluid replacement immediately to initiate a diuresis and avoid hypotension ■ From the other arm, obtain a sample for a direct antiglobulin test, plasma free hemoglobin, and repeat type and cross- match. Save a urine sample for hemoglobin testing.
  • 7. Acute hemolytic reactions : treatment ■ Avoid the use of Ringer's lactate solution because its content of calcium may initiate clotting of any blood remaining in the intravenous line. ■ Avoid dextrose-containing solutions because the dextrose may hemolyze any of the remaining red cells in the line. ■ The blood bank should be alerted immediately, and a search for clerical error should be instituted. ■ Every hospital has a protocol for evaluating transfusion reactions, which should be rigorously followed.
  • 8. Delayed hemolytic reactions ■ Delayed hemolysis results when the patient produces an antibody days following a blood transfusion ■ It presents 2 to 10 days following transfusion as jaundice and/or an unexpected fall in hemoglobin. ■ A delayed hemolytic transfusion reaction is confirmed by repeat antibody screening of the patient's plasma, which demonstrates the presence of a specific alloantibody that was not previously present.
  • 9. Delayed hemolytic reactions ■ Positive direct antiglobulin test for IgG with a positive eluate against the corresponding antigen will confirm the diagnosis. ■ It is therefore important to make the diagnosis, inform the patient of the name of the offending antigen, and maintain appropriate hospital and blood bank records. ■ Subsequent red cell transfusions should utilize blood that tests negative for the newly identified antigen. ■ No treatment is required in the absence of brisk hemolysis
  • 10. Febrile reactions ■ most common transfusion reaction is a febrile, nonhemolytic transfusion reaction (FNHTR). ■ The clinical manifestations : fever, often a chill, and sometimes mild dyspnea . within one to six hours after transfusion of red cells or platelets. ■ FNHTRs are benign, causing no lasting sequelae, but are uncomfortable and sometimes frightening to the patient. Furthermore, since fever, may be the sign of a severe, acute hemolytic transfusion reaction
  • 11. Febrile reactions ■ It is now clear that FNHTRs are commonly caused by cytokines, such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-alpha (TNFa), which are generated and accumulate during the storage of blood components ■ Treatment includes stopping the transfusion and excluding a hemolytic reaction or sepsis as the cause of fever. ■ Antipyretic therapy is given for symptomatic relief.These reactions are reduced with leukoreduction (reduce the number of leukocytes transfused)
  • 12. Acetaminophen and antihistamine premedication ■ A 2007 review summarized the data from studies that evaluated the use of premedication to decrease the incidence of FNHTRs or allergic transfusion reactions ■ Despite the fact that these medications are frequently ordered prior to transfusion, the authors concluded that there is no evidence to support the use of premedication with antihistamines and/or acetaminophen for the prevention of these reactions. TobianAA, King KE, Ness PM.Transfusion premedications: a growing practice not based on evidence.Transfusion 2007; 47:1089.
  • 13. Acetaminophen and antihistamine premedication ■ This conclusion was supported by a subsequent randomized, double-blind, placebo-controlled study of transfusion reactions in 315 hematology/oncology patients scheduled to receive leukocyte filtered blood products ■ Patients received acetaminophen 500 mg plus 25 mg diphenhydramine or matching placebos 30 minutes before transfusion and were monitored for the following four hours. ■ There was no significant difference in the overall risk of transfusion reactions between the treatment and placebo groups (1.4 versus 1.5 reactions/100 transfusions, respectively). Kennedy LD,Case LD, Hurd DD, et al.A prospective, randomized, double-blind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions.Transfusion 2008; 48:2285.
  • 14. Allergic and anaphylactic reactions ■ An anaphylactic, allergic, or anaphylactoid reaction to a blood transfusion can vary in severity from mild hives and itching to fatal anaphylaxis. manifested by shock, hypotension, angioedema, and respiratory distress ■ While more common with plasma and platelet transfusions, these reactions also may occur following red cell transfusion. ■ may occur within a few seconds to a few minutes following the initiation of a transfusion, It is the rapid onset that is characteristic of an ATR
  • 15. Allergic and anaphylactic reactions ■ Treatment is – Immediate cessation of the transfusion – Epinephrine intramuscularly – Resuscitation of hypotensive patients with intravenous fluids – Preparation, for possible administration, of an intravenous epinephrine – Airway maintenance, oxygenation – Vasopressors (eg, dopamine), if necessary
  • 16. Transfusion-associated lung injury ■ The presence of transfusion-associated acute lung injury (TRALI) should be suspected when dyspnea, bilateral non cardiogenic pulmonary edema, hypotension, and fever occur within six hours of completion of transfusion. ■ TRALI is the leading cause of transfusion-related mortality in the United States. ■ It is due primarily to the interaction between leukocytes from the recipient and anti-HLA antibodies or antigranulocyte antibodies from the donor. ■ Treatment is supportive.
  • 17. Infection ■ All donated blood is extensively screened for transfusion- transmitted infections; as a result, the risk of acquiring infection is extremely low ■ Each unit of blood administered is screened for a number of infections, including HIV, hepatitis B and C viruses. ■ Residual risk remains largely from "window period" donations, during the time when antigen and/or antibody are of such low level as to be undetectable by current techniques. ■ The risk of bacterial contamination of blood products is much greater than the risk of viral transmission. ■ Fever , hypotension, or other signs of sepsis should be investigated carefully in a patient who has received a transfusion.
  • 18. Circulatory overload ■ Transfusion-associated circulatory overload (TACO) may occur in children, although it is more common in adults. ■ Manifestations may begin near the end or within six hours of the transfusion. ■ Patients should be monitored closely during this time period for suggestive signs and symptoms, including dyspnea, tachycardia, and a wide pulse pressure, often with hypertension. ■ Patients deemed to be at risk for volume overload (such as those with impaired cardiac function) can be transfused at a slower rate and diuretic therapy (eg, furosemide 0.5 to 1 mg/kg per dose) may be used as a prophylactic measure and/or for treatment of symptoms.
  • 19. Circulatory overload ■ The symptoms of TACO are similar to those of TRALI. Distinguishing features are as follows: – TACO usually is associated with transfusion of a large volume of blood or a high rate of infusion; TRALI may occur with relatively small volumes at a slow rate – Hypertension is commonly seen in TACO but is uncommon in TRALI. – Fever is typically absent in TACO whereas TRALI is often associated with fever. – Brain natriuretic peptide (BNP) is often elevated in patients with TACO whereas it may be normal in TRALI. – Patients with TACO usually responds well to diuretic therapy; the response to diuretic therapy in patients with TRALI is variable.
  • 20. Metabolic toxicity ■ Hypocalcemia and/or hypoglycemia, which results from the infused citrate in the preservative solution. Newborns are at particular risk for this complication. ■ Hyperkalemia in patients who receive large volumes of blood (eg, exchange or massive transfusions) or irradiated blood (radiation increases cellular leakage of potassium). ■ Clinically significant accumulation of mannitol (a component of preservative solutions) in neonates who receive large volumes of blood may result in an osmotic diuresis. ■ Clinically significant accumulation of adenine (a component of preservative solutions) in neonates who receive large volumes of blood may cause nephrotoxicity.
  • 21. Graft-versus-host disease ■ Transfusion-associated graft-versus-host disease (TA-GVHD) is almost universally fatal and can be prevented by use of irradiated products. ■ It is caused by viable, competent donor lymphocytes ■ To reduce the risk ofTA-GVHD in patients requiring red blood cell transfusion, it is important to consider the immune status of the child and use irradiated products if indicated ■ Patients who are at risk forTA-GVHD include premature, low birth weight infants, infants and children with primary immunodeficiencies, organ transplant recipients, and patients receiving chemotherapy or other immunosuppressive therapy.
  • 22. Indication for irradiation of cellular blood components for the prevention of transfusion-associated graft-versus-host disease ■ Immunocompromised hematopoietic stem cell recipients or organ transplant recipients ■ Patients with hematologic disorders who will be undergoing marrow transplantation imminently ■ Intrauterine transfusion ■ Neonatal exchange transfusions ■ Premature, low birthweight neonates ■ Hodgkin lymphoma ■ Congenital cell-mediated immunodeficiencies
  • 23. Iron overload ■ Iron overload can be a significant problem in children who are transfused chronically. ■ As an example, the main cause of death in patients with thalassemia major is heart failure or fatal arrhythmia due to deposition of transfused iron in the heart. ■ Children who are at risk for iron overload can be treated with iron chelation therapy. It can reduce the damage produced by the life-long need for red cell transfusions in these children. ■ In addition, exchange transfusion rather than simple transfusion has been used in children with sickle cell disease, partly to reduce the risk of iron overload.

Editor's Notes

  1. Adsorption is the uptake of antibody by cells. Elution is the removal of antibody from cells. Absorption is the removal of antibody from serum, usually by adsorption.
  2. amino acid polypeptide secreted by the ventricles of the heart in response to excessive stretching of heart muscle cells (cardiomyocytes).
  3. Irradiated blood is blood that has been treated with radiation (by x-rays or other forms of radioactivity) to prevent TransfusionAssociated Graft-versus-Host Disease (TA-GvHD). All granulocyte and tissue type matched transfusions are routinely irradiated. Fresh frozen plasma and plasma products e.g. anti-D, albumin and immunoglobulin do not contain lymphocytes or cause TA-GvHD and therefore do not need to be irradiated.